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Long-Term Dynamics of Three Dimensional Telomere Profiles in Circulating Tumor Cells in High-Risk Prostate Cancer Patients Undergoing Androgen-Deprivation and Radiation Therapy

1
Cell Biology, Research Institute of Oncology and Hematology, University of Manitoba, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada
2
Manitoba Prostate Center, Cancer Care Manitoba, Section of Urology, Department of Surgery, University of Manitoba, Winnipeg, MB R3E 0V9, Canada
*
Authors to whom correspondence should be addressed.
Cancers 2019, 11(8), 1165; https://doi.org/10.3390/cancers11081165
Received: 5 July 2019 / Revised: 8 August 2019 / Accepted: 9 August 2019 / Published: 14 August 2019
(This article belongs to the Special Issue Liquid Biopsy for Cancer)
Patient-specific assessment, disease monitoring, and the development of an accurate early surrogate of the therapeutic efficacy of locally advanced prostate cancer still remain a clinical challenge. Contrary to prostate biopsies, circulating tumor cell (CTC) collection from blood is a less-invasive method and has potential as a real-time liquid biopsy and as a surrogate marker for treatment efficacy. In this study, we used size-based filtration to isolate CTCs from the blood of 100 prostate cancer patients with high-risk localized disease. CTCs from five time points: +0, +2, +6, +12 and +24 months were analyzed. Consenting treatment-naïve patients with cT3, Gleason 8-10, or prostate-specific antigen > 20 ng/mL and non-metastatic prostate cancer were included. For all time points, we performed 3D telomere-specific quantitative fluorescence in situ hybridization on a minimum of thirty isolated CTCs. The patients were divided into five groups based on the changes of number of telomeres vs telomere lengths over time and into three clusters based on all telomere parameters found on diagnosis. Group 2 was classified as non-respondent to treatment and the Cluster 3 presented more aggressive phenotype. Additionally, we compared our telomere results with the PSA levels for each patient at 6 months of ADT, at 6 months of completed RT, and at 36 months post-initial therapy. CTCs of patients with PSA levels above or equal to 0.1 ng/mL presented significant increases of nuclear volume, number of telomeres, and telomere aggregates. The 3D telomere analysis of CTCs identified disease heterogeneity among a clinically homogeneous group of patients, which suggests differences in therapeutic responses. Our finding suggests a new opportunity for better treatment monitoring of patients with localized high-risk prostate cancer. View Full-Text
Keywords: androgen deprivation therapy; radiotherapy; localized high-risk prostate cancer; circulating tumor cells; three-dimensional (3D) telomere profiling androgen deprivation therapy; radiotherapy; localized high-risk prostate cancer; circulating tumor cells; three-dimensional (3D) telomere profiling
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Wark, L.; Quon, H.; Ong, A.; Drachenberg, D.; Rangel-Pozzo, A.; Mai, S. Long-Term Dynamics of Three Dimensional Telomere Profiles in Circulating Tumor Cells in High-Risk Prostate Cancer Patients Undergoing Androgen-Deprivation and Radiation Therapy. Cancers 2019, 11, 1165.

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